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This version published online on October 18, 2007
Endocrinology, doi:10.1210/en.2007-1204
A more recent version of this article appeared on January 1, 2008
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Submitted on September 5, 2007
Accepted on October 11, 2007

Functional Development of the Ovarian Noradrenergic Innervation

Manuel Ricu, Alfonso Paredes, Monika Greiner, Sergio R Ojeda, and Hernan E Lara*

Laboratory of Neurobiochemistry, Department of Biochemistry and Molecular Biology. Faculty of Chemistry and Pharmaceutical Sciences, Universidad de Chile, Santiago 1, Chile and Oregon National Primate Research Center-Oregon Health and Science University, Portland, Oregon 97006.

* To whom correspondence should be addressed. E-mail: hlara{at}ciq.uchile.cl.

A substantial fraction of the noradrenergic innervation targeting the mammalian ovary is provided by neurons of the celiac ganglion. Although studies in the rat have shown that noradrenergic nerves reach the ovary near the time of birth, it is unknown how the functional capacity of this innervation unfolds during postnatal ovarian development. To address this issue we assessed the ability of the developing ovary to incorporate and release 3H-norepinephrine (3H-NE). Incorporation of 3H-NE was low during the first three weeks of postnatal life, but pharmacological inhibition of NE neuronal uptake with cocaine showed that an intact transport mechanism for NE into nerve terminals is already in place by the first week after birth. Consistent with this functional assessment, the mRNA encoding the NE transporter (NET) was also expressed in the celiac ganglion at this time. During neonatal-infantile development (PN day 5 to 20), the spontaneous, vesicle-independent outflow of recently taken-up NE was high, but the NE output in response to K+-induced depolarization was low. After PN20, spontaneous outflow decreased and the response to K+ increased markedly, reaching maximal values by the time of puberty. Tyramine-mediated displacement of NE stored in vesicles, which displace vesicular NE, showed that vesicle-dependent NE storage becomes functional by PN day 12, and that vesicular release increases during the juvenile-peripubertal phases of sexual development. These results indicate that vesicular release of NE from ovarian noradrenergic nerves begins to operate by the third week of postnatal life, becoming fully functional near the time of puberty.


Key words: ovary • development • norepinephrine release • norepinephrine transporter




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